He headed for America in 1535 enrolled in the expedition of Pedro de Mendoza and participated in the founding of Buenos Aires.
In 1539, Irala began to move the inhabitants of Buenos Aires to Asunción, and the city was abandoned by 1541.
He outlasted Charles V's appointee, Álvar Núñez Cabeza de Vaca, whom he had recalled to Spain for trial as a traitor.
During his rule, he had churches and public buildings erected, towns established, and the native population subjugated and distributed among the colonists in encomiendas.
Irala had 70 Guaraní concubines, and his surname fills several pages in the Asunción telephone directory.